Plenty of Spin and Bias in Cancer Drug Clinical Trials
January 15th, 2013 // 4:24 pm @ jmpickett
File this under ‘sweep it under the rug.’ It may be human nature to downplay unwanted or negative developments, but it is not considered to be good science. Nonetheless, some investigators have masked disappointing clinical trial results, such as missing primary endpoints and reporting toxicity, with selective and biased reporting for breast cancer treatments, according to a study in the Annals of Oncology.
Specifically, in one-third of all trials that failed to show a statistically significant benefit for a breast cancer medications being tested, the published studies emphasized less important outcomes in hopes of giving the results a positive spin. However, there was no association between industry or for-profit trial sponsorship and biased reporting of either efficacy or toxicity.
The researchers examined the results of 164 randomized, controlled Phase III trials of breast cancer treatments that were published between 1995 and 2011. They found 92 that were negative trials in which data did not demonstrate the medication had an effect on the primary endpoint. But in 59 percent of the negative trials, the authors used positive findings from secondary endpoints to cast the treatment in a positive light.
The researchers also found bias in the way adverse effects were discussed. Serious side effects, such as omitting mention in the abstract or conclusion, were found in 67 percent of the publications with both positive and negative findings. Moreover, trials with positive findings were twice as likely to underplay serious adverse effects compared with publications of negative studies.
However, some of the studies that were analyzed began before registration of clinical trials in such registries as ClinicalTrials.gov or clinicaltrialsregister.eu became mandatory. For those that were registered, the researchers found that some trials had primary endpoints changed between registration and when the findings were published.
“Among these trials, there was a trend towards change of the primary endpoint being associated with positive results, suggesting that it may be a strategy to make a negative trial appear positive,†the study authors write. “Trial registration does not necessarily remove bias in reporting outcomes, although it does make it easier to detect†(HERE IS THE STUDY)
They evaluated associations of bias with the Journal Impact Factor, which measures the frequency with which the average article in a journal has been cited in a given period of time; changes in the primary endpoint compared with information in ClinicalTrials.gov and funding sources. For recent trials, they determined whether the primary endpoints listed in ClinicalTrials.gov were the same as reported in abstracts or papers.
Why focus on trials that are testing breast cancer treatments? Because breast cancer is “the most common malignancy in women, has substantial mortality and is a cancer site with a large number of trials,†they authors write. They noted that neither disease-free survival nor progression-free survival have been shown as adequate surrogates for overall survival for women with breast cancer, but 83.5 percent of the trials used these endpoints.
